Changes in ovarian steroids alter brain functions, such as mood, anxiety, cognition and neural degeneration. However, the mechanisms by which these steroids alter neuronal function only now are being understood. The focus of our study is to determine the mechanisms by which progesterone and suckling stimuli interact in the lactating rat to provide neuroprotection against seizure induction and neuronal damage in the hippocampus (Hipc). This past year, we made the following observations 1) Although there is a small change in the N-Methyl-D-Aspartate (NMDA) receptor subunit protein expression in the Hipc, this change is unlikely enough to provide such dramatic resistance to seizure activation and damage. 2) The lactating rat displayed normal behavioral responses and immediate early gene (cFos) protein expression in response to direct application of an NMDA receptor agonist into the Hipc. These results suggest that the refractoriness to neuroexcitation in the Hipc of the la ctating rat is not due to a blunting of the post-synaptic NMDA response. Therefore, the lactating rat likely has a blunted presynaptic or afferent inputs into the Hipc. One of the candidates that may be involved is neuroactive steroids (NAS). We are presently mapping the mRNA and protein expression of 3?-hydroxysteroid dehydrogenase (3?-HSD), a NAS producing enzyme, in the rat brain. We have been able to determine that Hipc displays a high level of expression of the mRNA for 3?-HSD, while it has a low level of protein expression. This may suggest that the Hipc has the potential to produce large amounts of this NAS producing enzyme under specific conditions. An understanding of the mechanisms by which suckling and progesterone interact to provide resistance to hyperexcitation and neuronal damage in the lactating rat will provide important information for the understanding of changes in epileptic seizure activity in women during different reproductive stages. FUNDING Medical Research Foundation of Oregon PUBLICATIONS Grove KL, Smith MS. N-methyl-D-aspartate (NMDA) resistance in the hippocampus of the lactating rat is not due to a lack of a functional receptor system. Brain Res 814:157-163, 1998. Grove KL, Smith MS. 3?-hydroxysteroid dehydrogenase (3?-HSD) protein and mRNA distribution in the rat brain. In Endocrine Society Program & Abstracts 80th annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 493, 1998 (abstract #P3-527).